JC: CRYOSTAT-2 with Ross Davenport

Fibrin/platelet mesh

You might be aware that an exciting new trial has started called Cryostat-2.  This is exciting as it has the potential to improve patient outcomes, but also because it will involve all the Major Trauma Centres in England and 8 international centres, meaning it is an international, multi-centre, randomised controlled trial.


Bleeding accounts for 40% of all deaths from trauma, many within hours of injury. A recent NIHR Programme Grant for Applied Research found that approximately 7,780 people nationally suffer major haemorrhage each year, of whom an estimated 2,800 will die, at a total cost of nearly £150m to the NHS1. Fibrinogen is the key pro-coagulant factor needed for stable clot formation and the earliest clotting protein to fall during active major bleeding2. 25% of all trauma patients have abnormal blood clotting, which causes higher rates of major haemorrhage and four fold increased risk of death. This is . As what we know as Acute Traumatic Coagulopathy (ATC) and the Trauma-Induced Coagulopathy (TIC).  To clarify the difference, ATC is the coagulopathy that has been shown to occur as a result of tissue damage and the shock process, whereas TIC is ATC plus the effects of resuscitation efforts and inflammation. We know from research, the primary clotting abnormalities in trauma are increased clot breakdown and low fibrinogen levels. The CRASH-2 trial has shown that early treatment with tranexamic acid prevents clot breakdown and reduces mortality from trauma haemorrhage3. The results of a national observational trauma transfusion study4 found cryoprecipitate is administered late during the MHP, on average three hours after arrival.  Cryostat-1 showed that early replacement of fibrinogen with cryoprecipitate is able to rapidly restore fibrinogen levels and may halve mortality from trauma haemorrhage5.  Following on from this work, CRYOSTAT-2 will evaluate whether early administration of high-dose cryoprecipitate, in addition to standard major haemorrhage therapy, improves survival from traumatic bleeding.

To make cryoprecipitate (A.K.A. cryo), fresh frozen plasma is centrifuged and the precipitate, or denser material, is collected.  This volume is usually very small, so when you order cryo from your blood bank the bag you receive typically contains 4-6 pooled units.  Each unit contains about 400mg of fibrinogen, which means each bag you receive has around 2g of fibrinogen in it.  Cryo also has other useful bits in it, such as Factor VIII, von Willebrand factor, Factor XIII, and fibronectin.

Bag of Cryo
Bag of Cryo

We’ve already said that this is an international, multi-centre, randomised controlled trial, but let’s have a closer look at the details of the trial.

Trial Aims

This study will investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units – 6g fibrinogen) of cryoprecipitate on 28 day mortality.

The Trial Design

The study is sponsored by the Centre for Trauma Sciences at Queen Mary University of London and will be managed by the NHS Blood & Transplant Clinical Trials Unit with UK and International sites.

Inclusion criteria

Patients are eligible for this trial if:

1. The participant is judged to be an adult, aged 16 years or older in the UK (or according to local guidance) and has sustained severe traumatic injury.

2. The participant is deemed by the attending clinician to have active haemorrhage


3. Activation of the local major haemorrhage protocol for management of severe blood loss


4. At least one unit of any blood component.

Exclusion criteria

A patient will not be eligible for this study if he/she fulfils one or more of the following criteria:

1. The participant has been transferred from another hospital

2. The trauma team leader deems the injuries incompatible with life

3. More than three hours have elapsed from the time of injury.

Outcomes (n=1,568 patients)

Our primary outcome is all-cause mortality at 28 days.

Additional secondary measures include

1. All-cause mortality (including death from bleeding) at 6 hours, 24 hours, 6 months and 12 months from admission.

2. Death from bleeding at 6 hours and 24 hours.

3. Transfusion requirements, in numbers of units, for RBC, platelets, FFP & cryoprecipitate at 24 hours from admission, including pre-hospital transfusion.

4. Destination of participant at time of discharge from hospital.

5. Quality of life measures: EQ5D-5L and Glasgow Outcome Score at discharge and 6 months after injury.

6. Hospital resource use up to discharge or day 28, including blood transfusions, ventilator days, critical care and hospital length of stay.

7. Thrombotic events


This is a super exciting trial, and will help to inform how we treat this incredibly sick group of patients in the future.  If you want more information check out the Centre for Trauma Sciences website, the NHS Blood Transfusion page here, or the CRYOSTAT-2 study website here.





Campbell H, Stokes E, Bargo D, et al. Quantifying the healthcare costs of treating severely bleeding major trauma patients: a national study for England. Crit Care. 2015;19:276. [PubMed]
Hiippala S, Myllylä G, Vahtera E. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg. 1995;81(2):360-365. [PubMed]
CRASH-2 trial, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. [PubMed]
Stanworth S, Davenport R, Curry N, et al. Mortality from trauma haemorrhage and opportunities for improvement in transfusion practice. Br J Surg. 2016;103(4):357-365. [PubMed]
Curry N, Rourke C, Davenport R, et al. Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial. Br J Anaesth. 2015;115(1):76-83. [PubMed]

Cite this article as: Richard Carden, "JC: CRYOSTAT-2 with Ross Davenport," in St.Emlyn's, January 21, 2018, https://www.stemlynsblog.org/cryostat-2-ross-davenport/.

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